Many believe that hemolytic jaundice represents a greater risk for neurotoxicity than

nonhemolytic jaundice, although the reasons for this belief are not intuitively obvious,
assuming that total serum bilirubin levels are equal. In animal studies, bilirubin entry
into or clearance from the brain was not affected by the presence of hemolytic
anemia.

The technique of exchange transfusion, including adverse effects and complications,

is discussed extensively elsewhere. For more information, please consult Hemolytic
Disease of Newborn.

Management of infants with extreme jaundice

Numerous cases have been reported in which infants have been readmitted to
hospitals with extreme jaundice. In some cases, significant delays have occurred
between the time the infant was first seen by medical personnel and the actual
commencement of effective therapy.[42]

Any infant who returns to the hospital with significant jaundice within the first 1-2
weeks of birth should be immediately triaged with measurement of transcutaneous
bilirubin. High values should result in immediate initiation of treatment. If such a
measuring device is not available, or if the infant presents with any kind of
neurological symptoms, the infant should be put in maximally efficient phototherapy
as an emergency procedure, preferably by fast-tracking the infant to a NICU. Waiting
for laboratory results is not necessary before instituting such therapy because no
valid contraindications to phototherapy are possible in this scenario. Plans for an
exchange transfusion do not constitute an argument for delaying or not performing
phototherapy. Immediate benefit may be obtained within minutes, as soon as
conversion of bilirubin into water-soluble photoisomers is measurable (see
discussion above).

The need for intravenous hydration in such infants has been discussed. In the
absence of clinical signs of dehydration, no evidence suggests that overhydration is
helpful. If the infant is dehydrated, hydration should be given as clinically indicated.
However, if the infant is able to tolerate oral feeding, oral hydration with a breast milk
substitute is likely to be superior to intravenous hydration because it reduces
enterohepatic circulation of bilirubin and helps "wash" bilirubin out of the bowel.

Every hospital in which babies are delivered, or which has an emergency department
in which infants may be seen, should develop a protocol and triage algorithm for
rapid evaluation and management of jaundiced infants. The objective of such a
protocol should be rapid recognition of risk severity and reduction in the time to
initiate appropriate treatment.

Infants admitted with signs of intermediate to advanced acute bilirubin

encephalopathy (ABE) are in urgent need of treatment because reversibility may be
possible, even in such cases. The term "crash-cart approach" has been used as a
recommendation in such cases. The author, together with other European
colleagues, has published a series that included 6 patients with signs of ABE who
were urgently managed and appear to have escaped neurologic sequelae. [43]

In a review of the Kernicterus Registry, full recovery was noted in 8 of 11 cases

treated with a crash-cart approach, which included effective phototherapy plus
exchange transfusion; full recovery was not noted in cases in which delays had
occurred.[42] In the Kernicterus Registry, reversal was not observed in cases treated
with only phototherapy; the authors strongly recommend that exchange transfusion
be performed in such cases.[42] In the European study, reversal was also seen in 2
patients who did not receive exchange transfusion.[43] In one of these cases, IVIG
was used in lieu of exchange transfusion; in the other case, intensive phototherapy
and intravenous albumin were used.

Other therapies

In infants with breast milk jaundice, interruption of breastfeeding for 24-48 hours and
feeding with breast milk substitutes often helps to reduce the bilirubin level. Evidence
suggests that the simple expedient of supplementing feeds of breast milk with 5 mL
of a breast milk substitute reduces the level and duration of jaundice in breast milk–
fed infants. Because this latter intervention causes less interference with the
establishment of the breastfeeding dyad, the author prefers to use this approach
rather than complete interruption of breast feeding in most cases.
Oral bilirubin oxidase can reduce serum bilirubin levels, presumably by reducing
enterohepatic circulation; however, its use has not gained wide popularity. The same
may be said for agar or charcoal feeds, which act by binding bilirubin in the gut.
Bilirubin oxidase is not available as a drug, and for this reason, its use outside an
approved research protocol probably is proscribed in many countries.

Prophylactic treatment of Rh-negative women with Rh immunoglobulin has

significantly decreased the incidence and severity of Rh-hemolytic disease.

PENATALAKSANAAN OPERATIF

Surgical care is not indicated in infants with physiologic neonatal jaundice. Surgical
therapy is indicated in infants in whom jaundice is caused by bowel or external bile
duct atresia.

DIET

Breastfeeding concerns associated with neonatal jaundice are as follows:

 Incidence and duration of jaundice have increased as breastfeeding has

become more popular. The factors in breast milk that contribute to this
phenomenon are unclear. In selected infants, interruption of breastfeeding
and its replacement for 24-48 hours by a breast milk substitute may be
indicated. This decision should always be discussed in person with the mother
before implementation. The author's practice is now to first perform a trial of 5
mL of a hydrolyzed formula given after each breast meal. The author typically
tries this for at least 1-2 days, with follow-up of bilirubin values. Only if this is
unsuccessful does the author occasionally attempt interruption of breast
feeding.
 With increasing emphasis on breastfeeding, some new mothers may have
difficulty admitting (even to themselves) to a lack of success in establishing
lactation. Occasionally, infants of breastfeeding mothers are admitted to
hospitals with severe jaundice. They typically weigh significantly less than
 their birthweight at a time when they should have regained and surpassed
that weight. Presumably, the process is one of increased enterohepatic
circulation, as bilirubin is left longer in the proximal gut for lack of milk to bind
it and carry it onward and out. The author refers to this condition as lack-of-
breast-milk jaundice. These infants may respond dramatically to phototherapy
plus oral feedings of milk ad libitum

MEDIKAMENTOSA

Medications are not usually administered in infants with physiologic neonatal

jaundice. However, in certain instances, phenobarbital, an inducer of hepatic bilirubin
metabolism, has been used to enhance bilirubin metabolism. Several studies have
shown that phenobarbital is effective in reducing mean serum bilirubin values during
the first week of life. Phenobarbital may be administered prenatally in the mother or
postnatally in the infant.

In populations in which the incidence of neonatal jaundice or kernicterus is high, this

type of pharmacologic treatment may warrant consideration. However, concerns
surround the long-term effects of phenobarbital on these children. Therefore, this
treatment is probably not justified in populations with a low incidence of severe
neonatal jaundice. Other drugs can induce bilirubin metabolism, but lack of adequate
safety data prevents their use outside research protocols.

Intravenous immunoglobulin (IVIG) at 500 mg/kg has been shown to significantly

reduce the need for exchange transfusions in infants with isoimmune hemolytic
disease.[33] The mechanism is unknown but may be related to the way the immune
system handles red cells that have been coated by antibodies. Published experience
is still somewhat limited, but administration of immunoglobulin does not appear to be
likely associated with greater risks for the infant than an exchange transfusion.
Published data regarding efficacy are varied, perhaps suggesting that the specific
origin and characteristics of the IVIG preparation may play a role. Although
speculative, lack of efficacy of a specific IVIG product may warrant trial of one from a
different manufacturer or batch.
A new therapy currently under development consists of inhibition of bilirubin
production through blockage of heme oxygenase. This can be achieved through the
use of metal mesoporphyrins and protoporphyrins. Apparently, heme can be directly
excreted through the bile; thus, inhibition of heme oxygenase does not result in
accumulation of unprocessed heme. This approach may virtually eliminate neonatal
jaundice as a clinical problem. However, before the treatment can be applied on a
wide scale, important questions regarding the long-term safety of the drugs must be
answered. Also, in light of data suggesting that bilirubin may play an important role
as a free radical quencher, a more complete understanding of this putative role for
bilirubin is required before wholesale inhibition of its production is contemplated.